Anthropogenically elevated CO2 (eCO2) concentrations have been suggested to increase woody cover within tropical ecosystems through fertilization. The effect of eCO2 is built into Earth system models, although testing the relationship over long periods remains challenging. Here, we explore the relative importance of six drivers of vegetation change in western Africa over the past ~500,000 years (moisture availability, fire activity, mammalian herbivore density, temperature, temperature seasonality, CO2) by coupling past environmental change data from Lake Bosumtwi (Ghana) with global data. We found that moisture availability and fire activity were the most important factors in determining woody cover, whereas the effect of CO2 was small. Our findings suggest that the role of eCO2 effects on tropical vegetation in predictive models must be reconsidered.